ADENOVIRUSES

Adenoviruses
Structure and General Properties
• first isolated in 1953 in a human adenoid cell culture.
• Family: Adenoviridae
• Genome: linear, double-stranded DNA, DNA consist of 30 genes
• The virions are nonenveloped, icosahedrons CAPSID enclosing a core
DNA genome
•The capsid is comprised of 3 surface coat proteins
– Fibers
– Pentons
– Hexons
2
 Adenovirus structure
 The capsid is composed of 252 capsomers: 240 hexons (capsomers each surrounded by 6
other hexons capsomers) and 12 pentons (one at each vertex, each surrounded by 5
‘peripentonal’ hexons).

• Each penton consists of a penton base (composed of viral polypeptide III)

• The hexons each consist of three molecules of viral polypeptide II; they make up the
bulk of the icosahedron. Various other minor viral polypeptides occur in the virion.

3
 Adenoviruses
– penton base and fiber protein is the major adenovirus antigens
which is important for classification and disease diagnosis.
– The fiber contains the viral attachment proteins and can act as a
hemagglutinin.
– The penton base and fiber are toxic to cells.
• result in inhibition of cellular mRNA transport and protein
synthesis and tissue damage.
– They also carry type-specific antigens.
– Not easily affected by External environment, Low PH & proteolytic
enzymes and can replicate to high titer in the gastro intestinal
4
A. Electron micrograph of adenovirus virion with fibers B. Model of adenovirus virion with fibers.
The capsid is composed of 252 capsomers: 240 hexons and 12 pentons

The fibres can act as haemagglutinins and are the sites of attachment of the
virion to a host cell-surface receptor.

The hexons each consist of three molecules of viral polypeptide II; they make
up the bulk of the icosahedron. Various other minor viral polypeptides occur in
5
the virion.
 Capsid consist of 252 capsomeres (240 hexons and 12 pentons on the tops )
NOVIRUS STRUCTURE

Virion contain special protein-hemagglutinins (fibers) protruding from each of the 12

vertices of the capsid

6
 Adenoviruses ...
Classification
 Adenoviruses are grouped into four genera.
 All the human adenoviridae are classified in Mastadenoviruse genus.
 More than 100 serotypes
 more than 51 human sereotypes are known.
 Human adenoviruses are grouped A through F by
 DNA homologies and by physical, chemical and biological
properties.
This classification is based on ability to agglutinate blood
Viruses within a group tend to behave similarly with respect to
7
ADENOVIRUS – Classification Adapted
from Fields Virology
SUBGROUP SEROTYPES

A 12, 18, 31

B 3, 7, 11, 14, 34, 35

C 1, 2, 5, 6

D 8-10, 19, 20, 22-30, 36-39,

42-49

E 4

F 40, 41
• Serotype is mainly a result of differences in the penton base and
fiber protein, which determine the nature of tissue tropism and
disease.
• Common stereotypes are 1 -8, 11, 21, 35, 37, 40 & 41.
• The first human adenoviruses to be identified, numbered 1 to 7,
are the most common.
• Types 40 & 41 are enteric pathogens

9
 Pathogenesis and Immunity

• Adenoviruses infection may be asymptomatic or may result in various

diseases
• Common disorders caused by adenoviruses:
– respiratory tract infection - conjunctivitis (pinkeye),
– hemorrhagic cystitis, and gastroenteritis.
• Virus infects Mucoepithelial cells in the
– respiratory tract, gastrointestinal tract, and conjunctiva or cornea
• causing cell damage directly.
• Virus causes lytic, persistent, and latent infections in humans
– some strains can immortalize certain animal cells.
10
 Pathogenesis and Immunity
• The histologic hallmark of adenovirus infection is a
– dense, central intranuclear inclusion within an infected epithelial
cell that consists of viral DNA and protein.
– But adenovirus does not cause cellular enlargement (cytomegaly)
• Mononuclear cell infiltrates and epithelial cell necrosis are seen at
the site of infection.
• Viremia may occur after local replication of the virus
– with subsequent spread to visceral organs .
– This dissemination is more likely to occur in immunocompromised
patients than in immunocompetent people. 11
Adenoviral Inclusion Bodies
12
 Pathogenesis …

• The virus has a natural tendency (propensity) to become latent and

persist in lymphoid and other tissue such as
– adenoids, tonsils, and Peyer's patches, and can be reactivated in
immunosuppressed patients.
• Groups A and B adenoviruses are oncogenic in certain rodents
– but adenovirus transformation of human cells has not been
observed.
• Antibody is important for resolving lytic adenovirus infections
– protects the person from reinfection with the same serotype
– but not other serotypes.
13
• Cell-mediated immunity is important in limiting virus outgrowth
 Pathogenesis …
Mechanisms of Adenoviruses to evade host defenses:
• They encode small virus-associated RNAs (VA RNA) that prevent the
activation of viral protein synthesis inhibitor which is induced by the
interferon.
• The viral E3 and E1A proteins block apoptosis induced by cellular
responses to the virus or by T cell or cytokine (e.g., TNF-α) actions.
• Some strains of adenoviruses can inhibit CD8(+) cytotoxic T-cell
action by preventing proper expression of MHC I molecules and
therefore antigen presentation.

14
 Adenovirus pathogenesis

become latent
and persist in lymphoid 15
 Epidemiology of Adenoviruses
Disease/Viral Factors
• Resistant to inactivation by gastrointestinal tract and drying.
• Virus may cause asymptomatic shedding.

Transmission
• Direct contact via respiratory droplets and fecal matter, on hands,
on fomites (e.g., towels, contaminated medical instruments), close
contact, and inadequately chlorinated swimming pools.
• Fingers spread virus to eyes.

16
 Epidemiology of Adenoviruses
Who Is at Risk?

• Children younger than 14 years of age.

• People in crowded areas (e.g., daycare centers, military training

camps, swimming clubs).
Serotypes
• Adenoviruses 1 through 7 are the most prevalent serotypes.
• Most common serotypes in RI→1,2,3,5,7
• Gastroenteritis types →40,41

17
 Epidemiology …
• Infection with 1,2,5,6 (Group C) mainly during first 5 years of life-
– cause 5% to 10% of cases pediatric respiratory tract disease
– 3 and 7 during school years
– 4, 8 and 19 early adulthood
– Serotypes 3, 4 and 7 seem especially able to spread among
military recruits
• because of their close proximity and rigorous lifestyle.

18
 Time-course of infection
• Incubation period: 2-14 days
• Infective period continues for weeks
• Intermittent and prolonged rectal shedding
• Secondary attack rate within families up to 50%

19
 Clinical Syndromes
Disease Patient Population
Respiratory Diseases
Febrile, undifferentiated upper Infants, young children
respiratory tract infection
Pharyngoconjunctival fever Children, adults
Acute respiratory disease Military recruits
Pertussis-like syndrome Infants, young children
Pneumonia Infants, young children; military
recruits; immunocompromised
patients
Other Diseases
Acute hemorrhagic cystitis Children; bone marrow transplant
recipients
Epidemic keratoconjunctivitis Any age; renal transplant recipients
Gastroenteritis Infants, young children
Hepatitis Liver transplant recipients; other
immunocompromised patients
Meningoencephalitis Children; immunocompromised
patients

20
1. Respiratory system Clinical …

– common cold to pneumonia, croup, and bronchitis

• Upper respiratory infections: common cold (rhinitis);

– acute febrile pharyngitis and pharyngoconjunctival fever & tonsillitis

– Pharyngitis alone occurs in young children, particularly those

younger than 3 years,
– may mimic streptococcal infection.
– Pharyngoconjunctival fever occurs more often in outbreaks
involving older children.
• Lower respiratory infections: bronchitis; serotypes 3, 5 and 7
– acute respiratory disease & pneumonia

– More common in children 21

 ACUTE RESPIRATORY DISEASE
• A syndrome consisting of fever, cough, pharyngitis, and cervical
adenitis.
• Usually caused by adenovirus serotypes 4 and 7.
• OTHER RESPIRATORY TRACT DISEASES: Coldlike symptoms,
laryngitis, bronchiolitis.

• They can also cause a pertussis-like illness.

 Pharyngoconjunctival fever
 Headache, fever, malaise Conjunctivitis and Pharyngitis Cervical
adenopathy, rash and diarrhea
 also Main adenovirus types: 3, 4, 7, 14
 Epidemics in summer months.
 It transmitted trough Contaminated water in swimming pools,
fomites
 Clinical syndrome

2. Eye
• Acute follicular conjunctivitis & keratoconjunctivitis:
• Swimming pool conjunctivitis
• Epidemic keratoconjunctivitis may be an occupational hazard for
industrial workers.

24
Adenoviral Infections of the eye

Conjunctivitis caused by adenovirus cause pink eye

25
26
 Clinical syndrome
3. Gastroenteritis and Diarrhea
 Gastroenteritis ; mesenteric adenitis ; hepatitis ; appendicitis

• Adenovirus is a major cause of acute viral gastroenteritis;

– 15% of the cases of gastroenteritis in hospitalized patients are caused by
this virus.

• Adenovirus serotypes 40 to 42 have been grouped as enteric

adenoviruses (group F) and appear to be responsible for episodes
of diarrhea in infants.

27
 Clinical syndrome
 These enteric adenoviruses do not replicate in the same tissue
culture cells as other adenoviruses and rarely cause fever or
respiratory tract symptoms.
 Incubation period 3-10 days
 Diarrhea tends to last longer than other viruses that cause
Gastroenteritis (lasts for 10-14 days) E.g. Rotavirus
 May cause fatal disease in immuno - compromised patients

• More common Age <4 years

• Spread via fecal-oral route

28
 Laboratory Diagnosis
• Variety of clinical specimens depending on clinical syndrome-
– Nasopharygeal , conjunctival, stool, urine, tissue, etc.
• Isolation from pharyngeal site correlates better with current clinical
infection
• The presence of adenovirus in the throat of a patient with
pharyngitis is usually diagnostic
– if laboratory findings eliminate other common causes of
pharyngitis, such as Streptococcus pyogenes.

29
 Methods for diagnosis
• Direct demonstration of Virus
– Detection of viral DNA- PCR from variety of specimens
– Viral antigen detection- Immunifluorecence
– Electron microscopy and IEM- from stool extract but can’t identify
serotypes; used fro GIT infection only
• Culture
– Within 2 to 20 days, the virus causes a lytic infection with
characteristic inclusion bodies which can be seen in infected tissue
during histologic examination
– Enteric adenovirus serotypes 40 to 42 do not grow readily in
30
available cell cultures.
 Methods for diagnosis
• Serology: DFA, ELISA-soluble viral antigen
– A rise in antibody titer indicate recent infection (although not
its site and its nature)
– but absence does not exclude it, especially in babies.
– Serologic testing is rarely used except for epidemiologic
purposes or
– to confirm the significance of a fecal or upper respiratory tract
isolate by identifying its serotype.

31
 Treatment and prevention
Treatment
• No specific treatment
– There is no approved treatment for adenovirus infection.

Prevention
• Good hand washing
• Contact precautions
• Chlorination of water
• Disinfection or sterilization of ophthalmologic equipment
• Oral vaccine: restricted use, Live oral Adenovirus vaccine type 4 and 7
→ military recruits
32
Thank you!!!

33